Prioritizing regions of candidate genes for efficient mutation screening
Prioritizing regions of candidate genes for efficient mutation screening
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DOI：
10.1002/humu.20247
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发表时间：
2006-02-01
期刊：
影响因子：
3.9
通讯作者：
Stone, EM
中科院分区：
文献类型：
--
作者：
Braun, TA;Shankar, SP;Stone, EM
人类基因组完整序列的可用性极大地促进了疾病的寻找，导致了序列变异。事实上，速率限制步骤已经从候选基因的发现和表征转移到对人群的实际筛选以及随后对观察到的变异的解释。在这项研究中，我们测试了这样的假设：候选基因的某些片段比其他片段更有可能包含疾病，导致变异，并且这些片段可以通过生物信息学进行预测。开发了一种生物信息学技术，即注释区域优先级 (PAR)，用于根据保守的蛋白质功能域和蛋白质二级结构来预测基因的特定编码区域包含致病突变的可能性。该方法通过分析 710 个基因进行评估，这些基因总共包含 4,498 个先前识别的突变。仅筛选了 9% 的完整编码序列后，近 50% 的基因被识别为与疾病相关。 PAR 技术鉴定出 90% 的基因含有至少一种突变，而传统方法所需的筛选资源还不到 40%。这些结果表明，PAR 等优先策略可以通过更有效地利用筛查资源来加速疾病基因识别。
The availability of the complete sequence of the human genome has dramatically facilitated the search for disease,causing sequence variations. In fact, the rate,limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease,causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease-causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease-associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease-gene identification through more efficient use of screening resources.